The research interest of our lab currently focuses on the mechanism and regulation machinery of autophagy in higher eukaryotes. Autophagy is a lysosome-mediated degradation system that involves formation of a double membrane structure, called the autophagosome, and its subsequent fusion with lysosomes. It is involved in many biological processes in higher eukaryotes, including in defending against metabolic stress such as nutrient starvation, elimination of aggregate-prone proteins, decisions about cell death, and tissue homeostasis. The wealth of knowledge about C. elegans developmental biology and the availability of powerful experimental tools make C. elegans a good model for dissecting the autophagic machinery.

Studies in our lab have established C. elegans as a multicellular genetic model system to delineate the machinery, regulation and physiological functions of autophagy. We demonstrated that a variety of protein aggregates are selectively removed by autophagy during C. elegans embryogenesis, including germline P granule components in somatic cells. Using this model, we further performed genetic screens and identified several higher eukaryote-specific autophagy genes, epg-3, -4, -5 and -6, which define discrete genetic steps in the autophagy pathway.

The future research directions of our lab are as follow:

First, we are identifying novel autophagy genes. Several genetic screening approaches are being carried out, including isolating mutants with defective degradation of autophagy substrates.

Second, we are identifying genes required for degradation of specific types of protein aggregates. Characterization of such genes will help reveal how protein aggregates are selectively recognized and targeted to the autophagy machinery.

Third, we are studying how autophagy activity is regulated during animal development. We demonstrated that protein aggregates, which accumulate in the intestine in rpl-43 mutants, are degraded by autophagy during starvation. We are performing genetic and RNAi screens to identify mutations that suppress aggregate accumulation in rpl-43 mutants. We are also screening for suppressors of autophagy mutants. The genes identified will be analyzed to investigate how they integrate into the autophagy pathway.

Fourth, we are studying physiological functions of autophagy during animal development such as in germline cell death.

(Previewed as a leading edge finding in the same issue of Cell by Christina McPhee and Eric Baehrecke; selected as “Exceptional” for FACULTY OF 1000 Biology; highlighted by Felix Cheung in Nature China).

(Previewed as a leading edge finding in the same issue ofCell by Eric Baehrecke; selected as “Must Read” for FACULTY OF 1000 Biology; highlighted by Nathalie Le Bot in Nature Cell Biology 2009; 11, 246; highlighted by Jane Qiu in Nature China).